Does a triple combination have better activity than double combinations against multiresistant fungi? Experimental in vitro evaluation

In this study, the in vitro interactions of amphotericin B (AmB), voriconazole (VRC) and anidulafungin (AFG) in double and triple combinations against four species of multiresistant fungi ( Fusarium solani , Lomentospora prolificans , Scopulariopsis brevicaulis and Scopulariopsis brumptii ) were evaluated. In general, AmB combined with AFG was the most synergistic, especially against F. solani (7/8; 87.5%) when low concentrations of AmB were used, i.e. 0.125–0.5 µg/mL. The least active combination was AmB + VRC, with the lowest percentage of synergy against S. brevicaulis (2/11; 18.2%) and, in general, high concentrations of both antifungals were needed to achieve synergy. The triple combination was also highly synergistic against F. solani and S. brevicaulis , especially when the lowest concentrations of AmB were used, suggesting that use of combined therapies would reduce the toxicity of therapy. The triple combination was more effective than the double combinations in some cases, but not against all strains, suggesting that administration of three drugs is not always useful in the treatment of infections due to multiresistant fungi.